Development of a J paramyxovirus-based vaccine vector

Area of Science:

• Virology
• Vaccinology
• Molecular Biology

Background:

• Jilin paramyxovirus (JPV) is a negative-strand RNA virus.
• Recombinant JPV (rJPV) vectors show promise for vaccine development but can cause adverse effects.
• Further attenuation of rJPV vectors is needed for safer vaccine platforms.

Purpose of the Study:

• To develop a fully attenuated JPV-based vaccine vector.
• To assess the pathogenicity and immunogenicity of modified rJPV mutants.
• To evaluate the protective efficacy of the novel vector against Nipah virus.

Main Methods:

• Generated multiple rJPV mutants by deleting specific genes (SH, SP, X).
• Introduced L gene mutations into rJPV-∆3 to create rJPV-∆3-LW-L.
• Tested pathogenicity in mice and immunogenicity/efficacy in mice and hamsters using Nipah virus fusion (F) protein expression.

Main Results:

• rJPV lacking SH, SP, or SH/SP/X genes remained pathogenic.
• rJPV-∆3 with L gene mutations (rJPV-∆3-LW-L) was fully attenuated in mice.
• rJPV-∆3-LW-L expressing NiV-F induced anti-NiV-F antibodies and provided complete protection against lethal NiV challenge in hamsters.

Conclusions:

• A novel, fully attenuated intranasal JPV vaccine vector (rJPV-∆3-LW-L) was successfully developed.
• This vector demonstrates potential for effective intranasal immunization against viral pathogens like Nipah virus.
• The findings support the advancement of rJPV-based vaccine platforms.